Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib

Starting soon · Phase 1/Phase 2

Conditions studied: Lung Cancer (NSCLC), Lung Cancer (Non-Small Cell), Advanced Non-small-cell Lung Cancer

In brief

The goal of this clinical trial is to learn if Osimertinib plus Capivasertib works to treat EGFRm advanced non-small cell lung cancer (NSCLC) in participants with PIK3CA/AKT1/PTEN alterations after progression on first-line Osimertinib (monotherapy or plus chemotherapy). The main questions it aims to answer are: Part A: * Number of Dose-limiting toxicities (DLTs) * Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0) * Recommended combined dose (RCD) Part B:Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria. Participants will: Part A:Take Capivasertib twice daily from day 1 to 4 of a 7-day cycle, Osimertinib will be given orally QD(once daily) at 80 mg throughout the study treatment period. Part B: Take Osimertinib (80mg QD, continuously) and Capivasertib(RCD,orally BID from day1-day 4 in 7-day cycle , 4 days on /3 days off) till disease progression (PD) or unacceptable toxicity.

Key facts

Study ID: NCT07486648
Run by: Shanxi Province Cancer Hospital
People needed: 53
Starts: 2026-05-15
Expected to finish: 2028-12-31
Last updated by the study team: 2026-03-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Informed consent
Provision of signed and dated, written informed consent form (ICF) prior to any mandatory and non-mandatory study-specific procedures, sampling and analyses
Age
Male or female age ≥18 years at the time of signing the ICF.
Type of participant and disease characteristics
Histologically or cytologically confirmed non-squamous locally advanced or metastatic NSCLC which is not amenable to curative therapy.
Documented EGFR sensitive mutations (exon19 deletion, L858R mutation) prior to the first-line EGFR-TKI therapy.
Documented radiologic progression on first-line treatment with Osimertinib monotherapy or Osimertinib plus chemotherapy:
Participants treated with Osimertinib in the adjuvant setting can be included if progression occurred < 6 months after last dose.
Participants must be immunotherapy (i.e., programmed cell death protein 1 [PD-1] inhibitor, programmed cell death protein 1 ligand 1 [PD-L1] inhibitor, Cytotoxic T-lymphocyte associated protein 4 inhibitor) naïve in the metastatic setting.
Prior immunotherapy in the neoadjuvant or adjuvant setting is acceptable providing treatment was completed more than 6 months before metastatic/recurrent disease was diagnosed.
Mandatory provision of the required number of FFPE tumour tissue samples for PIK3CA mutations and/or AKT1 mutations and/or PTEN loss-of-function (LOF) mutations testing, which fulfils the following requirements:
Obtained following progression on previous Osimertinib monotherapy or Osimertinib plus chemotherapy as first-line treatment.
Specimen to meet the requirements defined in the Central Laboratory Manual and Diagnostic Testing Manual.
Have PIK3CA and/or AKT1 and/or PTEN alterations as determined by NGS testing by a sponsor designated central laboratory on tumour specimen collected following progression on prior Osimertinib treatment.
At least one lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with CT or MRI, which is suitable for accurate repeated measurements. If only one measurable lesion exists, it is acceptable to be used if baseline tumour assessment scans are done at least 14 days after the screening tumour specimen collection is performed.
Adequate bone marrow reserve and organ function as follows:
Absolute neutrophils count (ANC) ≥1.5x109/L.
Platelets count ≥100x109/L.
Haemoglobin (Hb) ≥90g/L.
Total bilirubin ≤1.5 times upper limit of normal (ULN) or ≤3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases.
Alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5ULN (or ≤5 ULN in the presence of liver metastases).
Serum Creatinine ≤1.5 ULN or creatinine clearance (CCr) ≥50mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Patients with hepatitis B virus (HBV) are only eligible for inclusion if they meet all the following criteria:

Where it is running

Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China
Shanxi Cancer Hospital — Taiyuan, Shanxi, China

Full record on ClinicalTrials.gov

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